PROJECT SUMMARY Human observational studies suggest ovarian hormones are involved in the neurobiology of bulimia nervosa (BN), specifically the symptom of binge eating: cumulatively, it appears that low estradiol (E2) or progesterone (P4) antagonized E2 are associated with increased binge eating. Problematic however, is that the effect of ovarian hormones on BN symptoms in humans has been inferred from animal studies and from changes in behavior occurring with presumed and measured levels of hormones during the menstrual cycle. Such observational studies cannot conclude a causal, mechanistic link. Moreover, why ovarian hormones influence symptom onset or fluctuation is unknown. Given that ovarian hormones, specifically E2, have pronounced effects on reward processing and neuropathways and neurotransmitters (e.g., dopamine) involved in reward, E2 may influence binge eating through its effect on reward processes that are altered in BN. Thus, we hypothesize BN represents a hormone sensitive phenotype and this sensitivity is displayed as an impaired reward response (i.e., reward-related inhibitory control deficits, heightened reward sensitivity, impaired delay discounting) in the context of low E2. Because women with BN represent a subgroup of the population with reduced dopamine activity, which is enhanced by E2, low E2 may promote reward-motivated behaviors such as binge eating via dopamine withdrawal. We propose this proof-of-concept study to examine our overarching hypothesis. We will complete a 3-month longitudinal, within-person experimental design that parallels animal models to directly manipulate ovarian hormones in females with BN (N = 10): temporarily inducing hypogonadism using a GnRH agonist and then addback E2 and P4 independently in a double-blind cross-over manner. During each phase of the manipulation, subjects will complete symptom reports of binge eating and behavioral tasks and questionnaires of reward processing and reward response. We will complete the following aims: 1): Quantify the direct effect of E2 and P4 on binge eating in women with BN; 2): Determine the effect of E2 on reward response (e.g., delay discounting) and related correlates (e.g., behavioral inhibition); 3): Examine the association between reward response and binge eating before and after E2 addback. If BN truly represents a hormone sensitive phenotype, we will see direct change in binge eating during the hormone challenge. Based on our previous work, we expect to see a beneficial effect of E2 and an exacerbating effect of P4. An experimental design is the only way we can confidently explore the direct impact of ovarian hormones on BN. This high-risk proposal has significant potential for high-reward. Successful completion of the aims will provide guidance in regard to if (and how) E2 and P4 directly affect binge eating in BN. This will provide the empirical direction needed for the investigators to complete a larger, hypothesis-driven mechanistic trial, in turn, providing direction for future research addressing neuroendocrine, neurobiological, and brain activity and function in BN.